For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the ... [more ▼]

For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBCT and CSS in patients with smoldering MM (SMM) and MM. Fifty-four of 212 patients (25.5%) had a negative CSS and a positive WBCT for osteolytic lesions (P<0.0001). Of 66 patients with SMM based on CSS, 12 (22.2%) had osteolytic lesions on WBCT. In comparison, WBCT failed to detect some bone destructions in the appendicular skeleton possibly due to limitations of the field of view. Presence of lytic bone lesions in WBCT was of borderline prognostic significance (P=0.051) for SMM patients, with a median time to progression of 38 versus 82 months for those without bone destructions. In conclusion, WBCT identifies significantly more sites of bone destruction than CSS. More than 20% of patients with SMM according to CSS have in fact active MM detectable with WBCT. On the basis of this and other studies, WBCT (either computed tomography (CT) alone or as part of a positron emission tomography-CT protocol) should be considered the current standard for the detection of osteolytic lesions in MM. [less ▲]

Multiple myeloma bone disease is a major cause of morbidity and mortality in multiple myeloma patients and persists even in patients in remission. Multiple myeloma bone disease is caused by an uncoupling ... [more ▼]

Multiple myeloma bone disease is a major cause of morbidity and mortality in multiple myeloma patients and persists even in patients in remission. Multiple myeloma bone disease is caused by an uncoupling of bone remodelling, with increased osteoclast activity and decreased osteoblast activity, culminating in lytic bone destruction. Bisphosphonates are the current standard-of-care but new therapies are needed. As the molecular mechanisms controlling multiple myeloma bone disease are increasingly understood, new therapeutic targets are extensively explored in the preclinical setting and initial clinical trials with novel compounds show promising results. In this review, we provide a comprehensive overview of the biology of multiple myeloma bone disease, summarise its current clinical management and discuss preclinical and clinical data on next generation therapies. [less ▲]

We present the case of a 48-year-old patient with a left adrenal incidentaloma found on computed tomography (CT) for which the diagnosis of pheochromocytoma was confirmed by a 24-hour urinary dosage of ... [more ▼]

We present the case of a 48-year-old patient with a left adrenal incidentaloma found on computed tomography (CT) for which the diagnosis of pheochromocytoma was confirmed by a 24-hour urinary dosage of norepinephrine. The 123I-mIBG scintigraphy showed a high uptake of 123I-mIBG in the left adrenal gland and, additionally, the single photon emission computed tomography combined with a low-dose CT (SPECT/CT) suggested the extension into the adrenal vein. The diagnostic CT and magnetic resonance images agreed with these findings and the subsequent surgery confirmed the vascular invasion. [less ▲]

Positron emission tomography combined with computed tomography (PET/CT) using RGD-based radiopharmaceuticals allows quantification of tumour expression of integrin αvβ3 in vivo. Integrins and, in particular, integrin αvβ3 are involved in numerous physiologic and pathologic processes, including angiogenesis. RGD-based radiopharmaceuticals targeting integrin αvβ3, expressed by activated endothelial cells, have been developed in order to quantify angiogenesis. However, integrin αvβ3 is also frequently expressed by tumour cells and/or tumour microenvironment cells, e.g., bone marrow derived cells and osteoclasts in bone. Upregulation of integrin αvβ3 by tumour cells promotes cell survival, proliferation, invasion, metastasis and resistance to treatment. Therefore, the PET signal related to RGD-based radiopharmaceuticals may not reflect angiogenesis only. Moreover, tumours may develop mechanisms other than angiogenesis to ensure blood supply such as vascular mimicry, vessel co-option and intussusceptive angiogenesis that might not be assessed with RGD PET/CT. In the setting of treatment assessment, a drop of the RGD PET signal certainly means tumour response (endothelial and/or tumour cell apoptosis and/or vessel normalisation). On the other hand, a stable or increased RGD PET signal may be related to absence of response or upregulation of integrin αvβ3 in adaptative response to therapy, promoting resistance. This review illustrates the complexity of the role of integrin αvβ3 in oncology and its role in non-oncologic diseases such as osteoarthtitis and cardiovascular diseases. [less ▲]

A majority of multiple myeloma patients present with osteolytic bone lesions that can cause bone pain, fractures or hypercalcaemia. Correct identification of these lesions is important in the initial ... [more ▼]

A majority of multiple myeloma patients present with osteolytic bone lesions that can cause bone pain, fractures or hypercalcaemia. Correct identification of these lesions is important in the initial assessment of the disease. <br />Although the radiological skeletal survey is the gold standard to detect bone osteolytic lesions, it may miss small bone lesions or lesions located in the spine or pelvis due to the superimposed images of soft tissues. These limitations propelled newer imaging techniques such as positron emission tomography combined with computed tomography (PET/CT) and magnetic resonance imaging (MRI) in the diagnosis of multiple myeloma. In addition, 18F-fluorodeoxyglucose PET/CT and MRI have prognostic value and can be used to monitor disease. <br />This review discusses the additional value of PET/CT and MRI in the management of MM. [less ▲]

OBJECTIVE: This work reports on musculoskeletal uptake of (18)F-FPRGD2, targeting the integrin alphavbeta3, in patients who had undergone (18)F-FPRGD2 positron emission tomography combined with computed ... [more ▼]

OBJECTIVE: This work reports on musculoskeletal uptake of (18)F-FPRGD2, targeting the integrin alphavbeta3, in patients who had undergone (18)F-FPRGD2 positron emission tomography combined with computed tomography (PET/CT) for oncologic purposes. METHODS: Whole-body (18)F-FPRGD2 PET/CT images of 62 cancer patients were retrospectively reviewed to detect foci of musculoskeletal (18)F-FPRGD2 uptake. For 37 patients, a FDG PET/CT performed in clinical settings was available. In each joint with an abnormal uptake, the maximum standardized uptake value (SUVmax) was estimated. RESULTS: A total of 260 musculoskeletal foci of (18)F-FPRGD2 uptake were detected. Most common sites of uptake were joints and discs (n = 160; 61.5 %), entheses (osteotendinous and osteoligamentous junctions; n = 55; 21.2 %) and recent fractures (n = 18; 6.9 %). In addition, 27 (10.4 %) miscellaneous foci were detected. Out of the 146 lesions for which a FDG PET was available, 63 % showed both (18)F-FPRGD2 and FDG uptake, 33.6 % did not show FDG avidity and 3.4 % showed only FDG uptake. The uptake intensity of the 92 lesions positive with (18)F-FPRGD2 and FDG was similar with both radiopharmaceuticals, but the target-to-background (blood pool or muscle) ratios were significantly higher with (18)F-FPRGD2 than with FDG (p < 0.0001). CONCLUSION: The (18)F-FPRGD2 uptake in joints, spine degenerative diseases and tendons was highly prevalent in our population. Up to one-third of (18)F-FPRGD2 foci showed no FDG uptake suggesting that (18)F-FPRGD2 signal may not be related to inflammatory angiogenesis only. [less ▲]

Multiple myeloma is the second most common hematologic malignancy and occurs most commonly in elderly patients. Almost all multiple myeloma patients develop bone lesions in the course of their disease or ... [more ▼]

Multiple myeloma is the second most common hematologic malignancy and occurs most commonly in elderly patients. Almost all multiple myeloma patients develop bone lesions in the course of their disease or have evidence of bone loss at initial diagnosis. Whole-body conventional radiography remains the gold standard in the diagnostic evaluation, but computed tomography, magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography are increasingly used as complementary techniques in the detection of bone lesions. Moreover, the number of lesions detected and the presence of extramedullary disease give strong prognostic information. These new techniques may help to assess treatment response in solitary plasmacytoma or in multiple myeloma. In this article, we review recent data on the different imaging techniques used at diagnosis and in the assessment of treatment response, and discuss some current issues. [less ▲]

PET/CT imaging could improve delineation of rectal carcinoma gross tumor volume (GTV) and reduce interobserver variability. The objective of this work was to compare various functional volume delineation ... [more ▼]

PET/CT imaging could improve delineation of rectal carcinoma gross tumor volume (GTV) and reduce interobserver variability. The objective of this work was to compare various functional volume delineation algorythms. [less ▲]

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that ... [more ▼]

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with Kras(G12D) to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy. [less ▲]